US6110706AExpiredUtility

Hepatitis B surface antigen vaccine

57
Assignee: MEDEVA HOLDINGS BVPriority: Jun 22, 1987Filed: Jun 7, 1995Granted: Aug 29, 2000
Est. expiryJun 22, 2007(expired)· nominal 20-yr term from priority
Inventors:Hans A. Thoma
C07K 14/445C12N 2770/32422C07K 2319/40A61K 38/00C07K 2319/735C12N 2770/32622C12N 15/62C12N 2730/10122Y10S530/826C12N 2740/15022C07K 2319/00A61P 31/20A61P 31/12C07K 14/005A61K 39/00C12N 15/00Y02A50/30
57
PatentIndex Score
6
Cited by
325
References
48
Claims

Abstract

HBV surface antigen particles, prepared by recombinant DNA technology are described, said particles being composed of epitopes from the group of surface peptides and/or core peptide of non-A, non-B hepatitis virus, hepatitis virus A and/or hepatitis virus B. Respective particles are especially characterized by a composition of different epitopes selected from pre-S and S peptides. There are also described DNA-sequences, plasmids and cell lines coding for respective HBV surface antigen particles as well as a new vaccine containing the same.

Claims

exact text as granted — not AI-modified
What is claimed is: 
     
       1. A polypeptide having an amino acid sequence selected from: Met-Glu-Asn-Asn-Pro-Leu-Gly-Phe-Phe-Pro-Asp-His-Gln-Leu-Asp-Pro-Ala-Phe-Arg-Ala-Asn-Thr-Ala-Asn-Pro-Asp-Trp-Asp-Phe-Asn-Pro-Ser-Xaa;   Met-Glu-Thr-Asn-Pro-Leu-Gly-Phe-Phe-Pro-Asp-His-Gln-Leu-Asp-Pro-Ala-Phe-Arg-Ala-Asn-Thr-Ala-Asn-Pro-Asp-Trp-Asp-Phe-Asn-Xaa; or   Met-Glu-Asn-Asp-His-Gln-Leu-Asp-Pro-Ala-Ser-Arg-Ala-Asn-Thr-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Asn-Xaa,   wherein Xaa is the amino acid sequence of amino acids 32 to 226 of an HBV S peptide.   
     
     
       2. The polypeptide of claim 1, wherein the amino acid sequence is: Met-Glu-Asn-Asn-Pro-Leu-Gly-Phe-Phe-Pro-Asp-His-Gln-Leu-Asp-Pro-Ala-Phe-Arg-Ala-Asn-Thr-Ala-Asn-Pro-Asp-Trp-Asp-Phe-Asn-Pro-Ser-Xaa.   
     
     
       3. The polypeptide of claim 1, wherein the amino acid sequence is: Met-Glu-Thr-Asn-Pro-Leu-Gly-Phe-Phe-Pro-Asp-His-Gln-Leu-Asp-Pro-Ala-Phe-Arg-Ala-Asn-Thr-Ala-Asn-Pro-Asp-Trp-Asp-Phe-Asn-Xaa.   
     
     
       4. The polypeptide of claim 1, wherein the amino acid sequence is: Met-Glu-Asn-Asp-His-Gly-Leu-Asp-Pro-Ala-Ser-Arg-Ala-Asn-Thr-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Asn-Xaa.   
     
     
       5. The polypeptide of claim 1, wherein the HBV S peptide is of the adw, ayw, adr, or ayr subtype. 
     
     
       6. The polypeptide of claim 1, wherein the HBV S peptide is of the adw subtype. 
     
     
       7. The polypeptide of claim 1, wherein the polypeptide is prepared by recombinant DNA processes from gene constructs in a cultured mammalian cell line. 
     
     
       8. The polypeptide of claim 7, wherein the cultured mammalian cell line is selected from VERO cells, 3T3 cells, C127 cells, L cells, or CHO cells. 
     
     
       9. The polypeptide of claim 7, wherein the cultured mammalian cell line comprises a gene construct which expresses a separate HBV S peptide. 
     
     
       10. A polypeptide having an amino acid sequence selected from: Yaa-Met-Glu-Asn-Asn-Pro-Leu-Gly-Phe-Phe-Pro-Asp-His-Gln-Leu-Asp-Pro-Ala-Phe-Arg-Ala-Asn-Thr-Ala-Asn-Pro-Asp-Trp-Asp-Phe-Asn-Pro-Ser-Xaa;   Yaa-Met-Glu-Thr-Asn-Pro-Leu-Gly-Phe-Phe-Pro-Asp-His-Gln-Leu-Asp-Pro-Ala-Phe-Arg-Ala-Asn-Thr-Ala-Asn-Pro-Asp-Trp-Asp-Phe-Asn-Xaa; or   Yaa-Met-Glu-Asn-Asp-His-Gln-Leu-Asp-Pro-Ala-Ser-Arg-Ala-Asn-Thr-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Asn-Xaa,   wherein Xaa is the amino acid sequence of amino acids 32 to 226 of an HBV S peptide and Yaa is the amino acid sequence of amino acids 1 to 31 of an HBV S peptide.   
     
     
       11. The polypeptide of claim 10, wherein the amino acid sequence is: Yaa-Met-Glu-Asn-Asn-Pro-Leu-Gly-Phe-Phe-Pro-Asp-His-Gln-Leu-Asp-Pro-Ala-Phe-Arg-Ala-Asn-Thr-Ala-Asn-Pro-Asp-Trp-Asp-Phe-Asn-Pro-Ser-Xaa.   
     
     
       12. The polypeptide of claim 10, wherein the amino acid sequence is: Yaa-Met-Glu-Thr-Asn-Pro-Leu-Gly-Phe-Phe-Pro-Asp-His-Gln-Leu-Asp-Pro-Ala-Phe-Arg-Ala-Asn-Thr-Ala-Asn-Pro-Asp-Trp-Asp-Phe-Asn-Xaa.   
     
     
       13. The polypeptide of claim 10, wherein the amino acid sequence is: Yaa-Met-Glu-Asn-Asp-His-Gln-Leu-Asp-Pro-Ala-Ser-Arg-Ala-Asn-Thr-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Asn-Xaa.   
     
     
       14. The polypeptide of claim 10, wherein the HBV S peptide is of the adw, ayw, adr, or ayr subtype. 
     
     
       15. The polypeptide of claim 10, wherein the HBV S peptide is of the adw subtype. 
     
     
       16. The polypeptide of claim 10, wherein the polypeptide is prepared by recombinant DNA processes from gene constructs in a cultured mammalian cell line. 
     
     
       17. The polypeptide of claim 16, wherein the cultured mammalian cell line is selected from VERO cells, 3T3 cells, C127 cells, L cells, or CHO cells. 
     
     
       18. The polypeptide of claim 16, wherein the cultured mammalian cell line comprises a gene construct which expresses a separate HBV S peptide. 
     
     
       19. A polypeptide having an amino acid sequence selected from: Met-Glu-Asn-Asn-Pro-Leu-Gly-Phe-Phe-Pro-Asp-His-Gln-Leu-Asp-Pro-Ala-Phe-Arg-Ala-Asn-Thr-Ala-Asn-Pro-Asp-Trp-Asp-Phe-Asn-Pro-Ser-Vaa-Waa;   Met-Glu-Thr-Asn-Pro-Leu-Gly-Phe-Phe-Pro-Asp-His-Gln-Leu-Asp-Pro-Ala-Phe-Arg-Ala-Asn-Thr-Ala-Asn-Pro-Asp-Trp-Asp-Phe-Asn-Vaa-Waa; or   Met-Glu-Asn-Asp-His-Gln-Leu-Asp-Pro-Ala-Ser-Arg-Ala-Asn-Thr-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Asn-Vaa-Waa,   wherein Vaa is selected from:   Leu-Asp-Pro-Ala-Leu-Asn-Ile;   Leu-Asp-Pro-Val-Val-Asn-Ile; or   Leu-Asp-Ser-Ser-Leu-Asn-Ile, and   wherein Waa is the amino acid sequence of amino acids 2 to 226 of an HBV S peptide.   
     
     
       20. The polypeptide of claim 19, wherein the amino acid sequence is: Met-Glu-Asn-Asn-Pro-Leu-Gly-Phe-Phe-Pro-Asp-His-Gln-Leu-Asp-Pro-Ala-Phe-Arg-Ala-Asn-Thr-Ala-Asn-Pro-Asp-Trp-Asp-Phe-Asn-Pro-Ser-Vaa-Waa.   
     
     
       21. The polypeptide of claim 19, wherein the amino acid sequence is: Met-Glu-Thr-Asn-Pro-Leu-Gly-Phe-Phe-Pro-Asp-His-Gln-Leu-Asp-Pro-Ala-Phe-Arg-Ala-Asn-Thr-Ala-Asn-Pro-Asp-Trp-Asp-Phe-Asn-Vaa-Waa.   
     
     
       22. The polypeptide of claim 19, wherein the amino acid sequence is: Met-Glu-Asn-Asp-His-Gln-Leu-Asp-Pro-Ala-Ser-Arg-Ala-Asn-Thr-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Asn-Vaa-Waa.   
     
     
       23. The polypeptide of claim 19, wherein Vaa is: Leu-Asp-Pro-Ala-Leu-Asn-Ile. 
     
     
       24. The polypeptide of claim 19, wherein Vaa is: Leu-Asp-Pro-Val-Val-Asn-Ile. 
     
     
       25. The polypeptide of claim 19, wherein Vaa is: Leu-Asp-Ser-Ser-Leu-Asn-Ile. 
     
     
       26. The polypeptide of claim 19, wherein the HBV S peptide is of the adw, ayw, adr, or ayr subtype. 
     
     
       27. The polypeptide of claim 19, wherein the HBV S peptide is of the adw subtype. 
     
     
       28. The polypeptide of claim 19, wherein the polypeptide is prepared by recombinant DNA processes from gene constructs in a cultured mammalian cell line. 
     
     
       29. The polypeptide of claim 28, wherein the cultured mammalian cell line is selected from VERO cells, 3T3 cells, C127 cells, L cells, or CHO cells. 
     
     
       30. The polypeptide of claim 28, wherein the cultured mammalian cell line comprises a gene construct which expresses a separate HBV S peptide. 
     
     
       31. A polypeptide having an amino acid sequence selected from: Met-Glu-Asn-Asn-Pro-Leu-Gly-Phe-Phe-Pro-Asp-His-Gln-Leu-Asp-Pro-Ala-Phe-Arg-Ala-Asn-Thr-Ala-Asn-Pro-Asp-Trp-Asp-Phe-Asn-Pro-Ser-Uaa-Xaa;   Met-Glu-Thr-Asn-Pro-Leu-Gly-Phe-Phe-Pro-Asp-His-Gln-Leu-Asp-Pro-Ala-Phe-Arg-Ala-Asn-Thr-Ala-Asn-Pro-Asp-Trp-Asp-Phe-Asn-Uaa-Xaa; or   Met-Glu-Asn-Asp-His-Gln-Leu-Asp-Pro-Ala-Ser-Arg-Ala-Asn-Thr-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Uaa-Xaa,   wherein Uaa is selected from:   Leu-Gly-Thr-Val-Asn-Pro-Val-Leu-Thr-Thr-Thr-Ser-Pro-Leu-Ser-Ser-Ile-Phe-Ser-Arg-Ile-Gly-Asp; or   Leu-Asp-Thr-Val-Asn-Pro-Val-Leu-Thr-Thr-Thr-Ser-Pro-Leu-Ser-Ser-Ile-Phe-Ser-Arg-Ile-Gly-Asp; and   wherein Xaa is the amino acid sequence of amino acids 32 to 226 of an HBV S peptide.   
     
     
       32. The polypeptide of claim 31, wherein the amino acid sequence is: Met-Glu-Asn-Asn-Pro-Leu-Gly-Phe-Phe-Pro-Asp-His-Gln-Leu-Asp-Pro-Ala-Phe-Arg-Ala-Asn-Thr-Ala-Asn-Pro-Asp-Trp-Asp-Phe-Asn-Pro-Ser-Uaa-Xaa.   
     
     
       33. The polypeptide of claim 31, wherein the amino acid sequence is: Met-Glu-Thr-Asn-Pro-Leu-Gly-Phe-Phe-Pro-Asp-His-Gln-Leu-Asp-Pro-Ala-Phe-Arg-Ala-Asn-Thr-Ala-Asn-Pro-Asp-Trp-Asp-Phe-Asn-Uaa-Xaa.   
     
     
       34. The polypeptide of claim 31, wherein the amino acid sequence is: Met-Glu-Asn-Asp-His-Gln-Leu-Asp-Pro-Ala-Ser-Arg-Ala-Asn-Thr-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Asn-Uaa-Xaa.   
     
     
       35. The polypeptide of claim 31, wherein the HBV S peptide is of the adw, ayw, adr, or ayr subtype. 
     
     
       36. The polypeptide of claim 31, wherein the HBV S peptide is of the adw subtype. 
     
     
       37. The polypeptide of claim 31, wherein the polypeptide is prepared by recombinant DNA processes from gene constructs in a cultured mammalian cell line. 
     
     
       38. The polypeptide of claim 37, wherein the cultured mammalian cell line is selected from VERO cells, 3T3 cells, C127 cells, L cells, or CHO cells. 
     
     
       39. The polypeptide of claim 37, wherein the cultured mammalian cell line comprises a gene construct which expresses a separate HBV S peptide. 
     
     
       40. A polypeptide having an amino acid sequence selected from: Met-Glu-Asn-Asn-Pro-Leu-Gly-Phe-Phe-Pro-Asp-His-Gln-Leu-Asp-Pro-Ala-Phe-Arg-Ala-Asn-Thr-Ala-Asn-Pro-Asp-Trp-Asp-Phe-Asn-Pro-Ser-Uaa-Vaa-Waa;   Met-Glu-Thr-Asn-Pro-Leu-Gly-Phe-Phe-Pro-Asp-His-Gln-Leu-Asp-Pro-Ala-Phe-Arg-Ala-Asn-Thr-Ala-Asn-Pro-Asp-Trp-Asp-Phe-Asn-Uaa-Vaa-Waa; or   Met-Glu-Asn-Asp-His-Gln-Leu-Asp-Pro-Ala-Ser-Arg-Ala-Asn-Thr-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Asn-Uaa-Vaa-Waa,   wherein Uaa is selected from:   Leu-Gly-Thr-Val-Asn-Pro-Val-Leu-Thr-Thr-Thr-Ser-Pro-Leu-Ser-Ser-Ile-Phe-Ser-Arg-Ile-Gly-Asp; or   Leu-Asp-Thr-Val-Asn-Pro-Val-Leu-Thr-Thr-Thr-Ser-Pro-Leu-Ser-Ser-Ile-Phe-Ser-Arg-Ile-Gly-Asp,   wherein Vaa is selected from:   Leu-Asp-Pro-Val-Leu-Asn-Ile;   Leu-Asp-Pro-Val-Val-Asn-Ile; or   Leu-Asp-Ser-Ser-Leu-Asn-Ile, and   wherein Waa is the amino acid sequence of amino acids 2 to 226 of an HBV S peptide.   
     
     
       41. The polypeptide of claim 40, wherein the amino acid sequence is: Met-Glu-Asn-Asn-Pro-Leu-Gly-Phe-Phe-Pro-Asp-His-Glu-Leu-Asp-Pro-Ala-Phe-Arg-Ala-Asn-Thr-Ala-Asn-Pro-Asp-Trp-Asp-Phe-Asn-Pro-Ser-Uaa-Vaa-Waa.   
     
     
       42. The polypeptide of claim 40, wherein the amino acid sequence is: Met-Glu-Thr-Asn-Pro-Leu-Gly-Phe-Phe-Pro-Asp-His-Glu-Leu-Asp-Pro-Ala-Phe-Arg-Ala-Asn-Thr-Ala-Asn-Pro-Asp-Trp-Asp-Phe-Asn-Uaa-Vaa-Waa.   
     
     
       43. The polypeptide of claim 40, wherein the amino acid sequence is: Met-Glu-Asn-Asp-His-Gln-Leu-Asp-Pro-Ala-Ser-Arg-Ala-Asn-Thr-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Ala-Asn-Uaa-Vaa-Waa.   
     
     
       44. The polypeptide of claim 40, wherein the HBV S peptide is of the adw, ayw, adr, or ayr subtype. 
     
     
       45. The polypeptide of claim 40, wherein the HBV S peptide is of the adw subtype. 
     
     
       46. The polypeptide of claim 40, wherein the polypeptide is prepared by recombinant DNA processes from gene constructs in a cultured mammalian cell line. 
     
     
       47. The polypeptide of claim 46, wherein the cultured mammalian cell line is selected from VERO cells, 3T3 cells, C127 cells, L cells, or CHO cells. 
     
     
       48. The polypeptide of claim 46, wherein the cultured mammalian cell line comprises a gene construct which expresses a separate HBV S peptide.

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